Abstract

Background

Interferon gamma release assays, including the QuantiFERON® TB Gold In Tube (QFT) have been shown to be accurate in diagnosing Mycobacterium tuberculosis infection. These assays however, do not discriminate between latent TB infection (LTBI)
and active TB disease.

Methods

We recruited twenty-three pulmonary TB patients and 34 household contacts from Cape
Town, South Africa and performed the QFT test. To investigate the ability of new host
markers to differentiate between LTBI and active TB, levels of 29 biomarkers in QFT
supernatants were evaluated using a Luminex multiplex cytokine assay.

Results

Eight out of 29 biomarkers distinguished active TB from LTBI in a pilot study. Baseline
levels of epidermal growth factor (EGF) soluble CD40 ligand (sCD40L), antigen stimulated
levels of EGF, and the background corrected antigen stimulated levels of EGF and macrophage
inflammatory protein (MIP)-1β were the most informative single markers for differentiation
between TB disease and LTBI, with AUCs of 0.88, 0.84, 0.87, 0.90 and 0.79 respectively.
The combination of EGF and MIP-1β predicted 96% of active TB cases and 92% of LTBIs.
Combinations between EGF, sCD40L, VEGF, TGF-α and IL-1α also showed potential to differentiate
between TB infection states. EGF, VEGF, TGF-α and sCD40L levels were higher in TB
patients.

Conclusion

These preliminary data suggest that active TB may be accurately differentiated from
LTBI utilizing adaptations of the commercial QFT test that includes measurement of
EGF, sCD40L, MIP-1β, VEGF, TGF-α or IL-1α in supernatants from QFT assays. This approach
holds promise for development as a rapid diagnostic test for active TB.